4-aminopyridine, a specific blocker of K+ channels, inhibited inward Na+ current in rat cerebellar granule cells

The effects of 4-aminopyridine (4-AP), a specific blocker of outward K+ current, on voltage-activated transient outward K+ current (I-K(A)) and inward Na+ current (I-Na) were investigated on cultured rat cerebellar granule cells using the whole cell voltage-clamp technique. At the concentration of 1-5 mM, 4-AP inhibited both I-K(A) and I-Na. It reduced the amplitude of peak Na+ current without significant alteration of the steady-state activation and inactivation properties. The inhibitory effect was not enhanced by repeated depolarizing pulses (0.5 or 0.1 Hz), suggesting that the binding affinity of 4-AP on Na+ channels is state-independent. In contrast, the effect of 4-AP on Nac channels appeared to be voltage-dependent, the weaker inhibition occurred at more depolarization. Moreover, 4-AP slowed both the activation and inactivation kinetics of Na+ current. These effects were similar to those induced by alpha-scorpion toxin and sea anemone toxins on Na+ channels in other cell model. Our data demonstrate for the first time that 4-AP is able to black not only A-type K+ channels, but also Na+ channels in rat cerebellar granule cells. It is concluded that the inhibition exerted by 4-AP on Na+ current likely differs from that provoked by local anesthetics. The possibility that the binding site of neurotoxin receptor 3 may be involved is discussed. (C) 2000 Elsevier Science B.V. All rights reserved.